title: The CD14(+/low)CD16(+) monocyte subset is more susceptible to spontaneous and oxidant-induced apoptosis than the CD14(+)CD16(-) subset.
abstract: Human monocytes can be classified into two subsets with distinctive characteristics. In this study, we report a difference in apoptotic potential between these two subsets with CD14(+/low)CD16(+) monocytes being more susceptible than CD14(+)CD16(-) monocytes to undergo spontaneous apoptosis and apoptosis induced by reactive oxygen species (ROS). By global transcriptomic and proteomic approaches, we observed that CD14(+/low)CD16(+) monocytes expressed higher levels of pro-apoptotic genes and proteins such as TNFα, caspase 3, Bax and cytochrome c and showed more caspases 3 and 7 activities. They also exhibited greater aerobic respiration resulting in a higher production of ROS from the mitochondria. CD14(+)CD16(-) monocytes, in contrast, showed higher expression of glutathione (GSH)-metabolizing genes such as GSH peroxidase and microsomal GSH S-transferase and were more resistant to oxidative stress than CD14(+/low)CD16(+) monocytes. The apoptosis of CD14(+/low)CD16(+) monocytes was ROS dependent as reducing ROS levels significantly reduced cell death. This is the first report of a differential apoptotic propensity of human monocyte subsets, and gaining a better understanding of this process may help to provide a better understanding of the roles of these subsets during homeostasis and under pathological conditions, particularly in situations in which high levels of oxidants are present.
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Biopolis, Singapore.
authors.forename: C
authors.initials: C
authors.lastname: Zhao
authors.forename: Y-C
authors.initials: YC
authors.lastname: Tan
authors.forename: W-C
authors.initials: WC
authors.lastname: Wong
authors.forename: X
authors.initials: X
authors.lastname: Sem
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: H
authors.initials: H
authors.lastname: Han
authors.forename: S-M
authors.initials: SM
authors.lastname: Ong
authors.forename: K-L
authors.initials: KL
authors.lastname: Wong
authors.forename: W-H
authors.initials: WH
authors.lastname: Yeap
authors.forename: S-K
authors.initials: SK
authors.lastname: Sze
authors.forename: P
authors.initials: P
authors.lastname: Kourilsky
authors.forename: S-C
authors.initials: SC
authors.lastname: Wong
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D020869:Gene Expression Profiling; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D009000:Monocytes / Q000145:classification* / Q000276:immunology / Q000378:metabolism; D018384:Oxidative Stress; D020543:Proteome / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D018950:Lipopolysaccharide Receptors; D020543:Proteome; D017382:Reactive Oxygen Species; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D053148:Caspase 3; D053179:Caspase 7